Rapid measurement of SARS-CoV-2 spike T cells in whole blood from vaccinated and naturally infected individuals

• Published in: The Journal of clinical investigation Vol. 131; no. 17; pp. 1 - 13
• Main Authors: Tan, Anthony T, Lim, Joey Me, Le Bert, Nina, Kunasegaran, Kamini, Chia, Adeline, Qui, Martin Dc, Tan, Nicole, Chia, Wan Ni, de Alwis, Ruklanthi, Ying, Ding, Sim, Jean Xy, Ooi, Eng Eong, Wang, Lin-Fa, Chen, Mark I-Cheng, Young, Barnaby E, Hsu, Li Yang, Low, Jenny Gh, Lye, David C, Bertoletti, Antonio
• Format: Journal Article
• Language: English
• Published: United States American Society for Clinical Investigation 01.09.2021
• Subjects: Adult; Antibodies; Antigens; Asymptomatic; Biomedical research; BNT162 Vaccine; Cell activation; Coronaviruses; COVID-19; COVID-19 - blood; COVID-19 - immunology; COVID-19 - prevention & control; COVID-19 vaccines; COVID-19 Vaccines - administration & dosage; Cytokines; Enzyme-linked immunosorbent assay; Female; Humans; Humoral immunity; Immunity, Cellular - drug effects; Infections; Interleukin 2; Laboratories; Lymphocytes; Lymphocytes T; Male; Middle Aged; Pandemics; Peptides; Proteins; SARS-CoV-2 - immunology; SARS-CoV-2 - metabolism; Severe acute respiratory syndrome coronavirus 2; Spike Glycoprotein, Coronavirus - blood; Spike Glycoprotein, Coronavirus - immunology; Spike protein; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Vaccination; Viral infections; γ-Interferon; COVID-19; Adaptive immunity; Immunology; Cytokines; T cells
• DOI: 10.1172/JCI152379
• ISSN: 1558-8238; 0021-9738

Defining the correlates of protection necessary to manage the COVID-19 pandemic requires the analysis of both antibody and T cell parameters, but the complexity of traditional tests limits virus-specific T cell measurements. We tested the sensitivity and performance of a simple and rapid SARS-CoV-2 spike protein-specific T cell test based on the stimulation of whole blood with peptides covering the SARS-CoV-2 spike protein, followed by cytokine (IFN-γ, IL-2) measurement in different cohorts including BNT162b2-vaccinated individuals (n = 112), convalescent asymptomatic and symptomatic COVID-19 patients (n = 130), and SARS-CoV-1-convalescent individuals (n = 12). The sensitivity of this rapid test is comparable to that of traditional methods of T cell analysis (ELISPOT, activation-induced marker). Using this test, we observed a similar mean magnitude of T cell responses between the vaccinees and SARS-CoV-2 convalescents 3 months after vaccination or virus priming. However, a wide heterogeneity of the magnitude of spike-specific T cell responses characterized the individual responses, irrespective of the time of analysis. The magnitude of these spike-specific T cell responses cannot be predicted from the neutralizing antibody levels. Hence, both humoral and cellular spike-specific immunity should be tested after vaccination to define the correlates of protection necessary to evaluate current vaccine strategies.